Structure-function relations in myoglobins and hemoglobins are to be correlated in terms of sequences, interactions with ligands, effectors and various ions, and internal evidences of conformational changes. Reactivity measures for the hemoglobins will deal with the known effectors and the protein groups potentially involved in their interactions. Closely related protein species will be used for residue by residue comparisons as much as possible. Natural components are to be augmented gradually by labeled or altered components prepared by semisynthesis. In addition to the systematic binding studies for ligands by classical techniques the comparisons will be made in terms of nuclear magnetic resonance measurements in several modes with 1H, 2H, and 13C nuclei. These measurements will reflect binding phenomena as well as conformational transitions and motional behavior. For the myoglobins these studies are potentially made in great detail with close reference to the crystalline structure and a search for parallels and contrasts with the tertiary changes undergone by hemoglobins. The sequence data obtained for the myoglobins will give information on evolutionary relationships and indicate the most important aspects of structural conservation related to various functions. The semisynthetic methods will be applied gradually to biologically important peptide systems as the opportunity arises. A theoretical treatment has been refined for the production of electrostatic interaction behavior and pK values in globular proteins and its application to the myoglobin, hemoglobin and related proteins will be tested. An extensive restricted diffusion and jump model theory has been developed to analyze motions of protein side chains and is being tested with myoglobin studies utilizing 13C NMR.